DESCRIPTION: The PI has a long-standing interest in fatty acid binding proteins. The present proposal hinges on studies of two such proteins, aP2 and KLBP. The hypothesis of this proposal is that aP2, but not KLBP, stimulates gene transcription by delivering lipid ligands to the lipid activated transcription factor PPAR gamma 2. Since aP2 knock-out mice develop obesity only on a high fat diet, and such obesity is uncoupled from insulin resistance and TNF alpha production, the PI hypothesizes that aP2 affects the development of obesity by trafficking hydrophobic ligand to nuclear transcription factors, thereby regulating the expression of genes whose products are involved in the development of insulin resistance and NIDDM. The PI proposes the following set of experiments to test the hypothesis: A. To express wild-type and lipid binding proteins in aP2 and KLBP null mice, and to assess the expression of TNF alpha and the development of insulin resistance in these mice under different dietary conditions; B. To characterize the interactions between aP2 and PPAR gamma 1 and 2 in response to thiazolidinediones and polyunsaturated fatty acids; and C to examine lipid trafficking in adipocytes derived from KLBP and ap2 null mice using retroviral expression techniques.